HVTN 204, RV-172, and IAVI-001 are being conducted with the Vaccine Research Center (VRC), and sponsored by the Division of AIDS (DAIDS), U.S. National Institute of Allergy and Infectious Diseases (NIAID) in order to qualify a six-plasmid multiclade HIV-1 DNA vaccine boosted by a multiclade HIV-1 recombinant adenovirus-5 vector (rAd5) vaccine for future efficacy evaluation. These studies are being conducted by three independent trial networks and each network consists of non-overlapping national and international partnerships to execute vaccine clinical trials. The main objective of these three trials taken together is to attain safety and immunogenicity data sufficient to proceed with efficacy testing within each of the networks. Phase II safety data that support the safety of this prime-boost vaccine approach as well as immunogenicity data that shows distinct improvement over candidates which have been, or are, in efficacy trials are needed to move into an efficacy trial. All three networks are part of the Partnership for AIDS Vaccine Evaluation (PAVE). PAVE is a consortium of organizations that are actively involved in HIV vaccine clinical research and development and consists of the DAIDS, VRC, NIAID-sponsored HVTN and USMHRP, the Centers for Disease Control and Prevention (CDC), and IAVI. This consortium is charged with bringing their cumulative global expertise to bear on the conduct of large-scale efficacy trials. HVTN, USMHRP and IAVI, working closely with international host site investigators from each of the countries to implement the studies, wrote the protocols HVTN 204, RV 172 and IAVI-V001, respectively. It is crucial that all three trials, although independent from one another, are planned and implemented with sufficient harmonization to guarantee compatibility of the respective data sets for aggregated analyses. The three studies will provide data from the U.S. and countries in Eastern Africa, the Caribbean, South America, and the Southern Africa. The regions are defined as follows: 1. United States of America, South America, and the Caribbean in HVTN 204 2. Southern Africa in HVTN 204 3. Eastern Africa in RV 172 and IAVI-V001 All three trials will be conducted in accordance with current Good Clinical Practice (cGCP), International Conference on Harmonization (ICH) guidelines and the revised U.S. Code of Federal Regulations-21 and 45 CFRs. The U.S. FDA will be the regulatory agency granting the IND application for the three studies. However, all country specific regulations for approval, implementation, and reporting will be followed as applicable. Harmonization of the three trials will continue throughout the implementation period of the studies with continued communication and meetings, as needed, to discuss any elements of one trial that may affect and/or trigger modification of all three trials. Although safety management of each trial will be independently followed for each protocol, there will be a continued and open exchange of safety information channeled through the common DAIDS Medical Officer for all three trials and the vaccine developer. In addition, members of each network will be participate in other network's protocol safety reviews teams (PSRTs). Phase I components (IAVI-V001 and Part A of RV-172) will be focused on safety and immunogenicity of two dose levels of rAd5 in participants with a broad range of preexisting Ad5 antibody titers, with and without prior DNA priming. These studies will complement VRC 006 and HVTN 054 to determine whether additional effort should be given to the evaluation of the 1011 dose of rAd5 or move to alternative Ad serotypes as HIV gene vectors. Together the studies are powered to detect small differences in safety and tolerability (between vaccine and placebo); and RV 172 and HVTN 204, the Phase II studies, are powered individually to detect small differences in immunogenicity between the vaccine and placebo arms. The test-of-concept efficacy trial, PAVE-100, is now well along in the planning and protocol development process. Estimated start is during FY-07,